Transcranial direct current stimulation as a potential remyelinating therapy: Visual evoked potentials recovery in cuprizone demyelination

Aims: Non-invasive neuromodulation by transcranial direct current stimulation (tDCS), owing to its reported beneficial effects on neuronal plasticity, has been proposed as a treatment to promote functional recovery in several neurological conditions, including demyelinating diseases like multiple sclerosis. Less information is available on the effects of tDCS in major pathological mechanisms of multiple sclerosis, such as demyelination and inflammation. To learn more about the latter effects, we applied multi-session anodal tDCS in mice exposed to long-term cuprizone (CPZ) diet, known to induce chronic demyelination. Methods: Visual evoked potentials (VEP) and motor performance (beam test) were employed for longitudinal monitoring of visual and motor pathways in 28 mice undergoing CPZ diet, compared with 12 control (H) mice. After randomization, anodal tDCS was applied for 5 days in awake, freely-moving surviving animals: 12 CPZanodal, 10 CPZ-sham, 5H-anodal, 5 h-sham. At the end of the experiment, histological analysis was performed on the optic nerves and corpus callosum for myelin, axons and microglia/macrophages. Key findings: CPZ diet was associated with significantly delayed VEPs starting at 4 weeks compared with their baseline, significant compared with controls at 8 weeks. After 5-day tDCS, VEPs latency significantly recovered in the active group compared with the sham group. Similar findings were observed in the time to cross on the beam test Optic nerve histology revealed higher myelin content and lower microglia/macrophage counts in the CPZAnodal group compared with CPZ-Sham. Significance: Multiple sessions of anodal transcranial direct current stimulation (tDCS) in freely moving mice induced recovery of visual nervous conduction and significant beneficial effects in myelin content and inflammatory cells in the cuprizone model of demyelination. Altogether, these promising findings prompt further exploration of tDCS as a potential therapeutic approach for remyelination.